Thrombotic microangiopathy associated with Valproic acid toxicity

Area of Science:

• Nephrology
• Hematology
• Toxicology

Background:

• Thrombotic microangiopathy (TMA) is a critical condition characterized by endothelial damage and microvascular thrombi.
• Drug-induced TMA (DI-TMA) arises from drug exposure, either through antibodies or direct toxicity, with known associations to certain immunosuppressants and chemotherapeutics.
• Valproic acid has not previously been linked to DI-TMA.

Observation:

• An adolescent male with epilepsy experienced hepatic dysfunction and subsequent severe metabolic lactic acidosis and multiorgan failure during valproic acid therapy.
• The patient developed progressive anemia, thrombocytopenia, hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and acute kidney injury, indicating TMA.
• Thrombotic thrombocytopenic purpura was ruled out due to sufficient ADAMTS13 activity.

Findings:

• Discontinuation of valproic acid led to the reversal of anemia, thrombocytopenia, and normalization of LDH and haptoglobin levels.
• These clinical improvements strongly support valproic acid toxicity as the causative agent for the observed TMA.
• This represents the first documented case of DI-TMA associated with valproic acid toxicity.

Implications:

• This case expands the spectrum of known drug-induced thrombotic microangiopathies.
• Clinicians should consider valproic acid as a potential cause of TMA in patients presenting with compatible symptoms.
• Early recognition and drug withdrawal are crucial for managing valproic acid-induced TMA.